Plasma Elevations of Two Brain Proteins Found in Fighters Exposed to Repeated Head Blows

Plasma concentrations of two brain proteins — neurofilament light chain (NFL) and tau — are elevated in individuals exposed to repetitive head impacts, according to an analysis of longitudinal results from a cohort of the Cleveland Clinic-led Professional Fighters Brain Health Study.

“We found that higher levels of both proteins may be associated with repetitive head trauma,” says lead investigator Charles Bernick, MD, MPH, who presented the findings at the American Academy of Neurology’s Sports Concussion Conference in Jacksonville, Florida, in July. “This is part of a study to ultimately determine whether professional fighters are at risk of long-term neurological complications, and which are at greatest risk. These findings set the stage for research on how these proteins may be used to monitor traumatic brain injury (TBI) and its consequences over time.”

NFL and tau are components of nerve fibers that are detectable in blood when the fibers are injured. While both proteins had been viewed as potential markers of acute neural injury, less had been known about their application in chronic mild TBI, explains Dr. Bernick, Associate Director of Cleveland Clinic Lou Ruvo Center for Brain Health in Las Vegas.

Up to 5 years of biomarker, imaging and cognitive monitoring

To better assess that question, Dr. Bernick and colleagues evaluated a cohort of active and retired professional fighters (boxers and mixed martial arts combatants) and controls not involved in combat sports, all of whom participate in the larger Professional Fighters Brain Health Study. The researchers obtained blood samples from all participants at baseline and at annual study visits for up to five years. Protein concentrations were analyzed in blinded fashion using the ultrasensitive Simoa platform.

Participants also underwent brain MRI and computerized cognitive testing on an annual basis.

The cohort consisted of:

• 291 active fighters (mean age, 29.9 years)
• 44 retired fighters (mean age, 45.3 years)
• 103 non-fighter controls (mean age, 29.6 years)

Outcomes of interest included baseline differences in the blood markers among the groups, the relationship of blood marker levels with the amount and timing of repetitive head impact exposure, changes in marker levels over time, and the relationship of marker levels with MRI volumetric measurements and cognitive test performance.

Main study findings

Key results reported by Dr. Bernick at the concussion conference included the following:

• Levels of both NFL and tau were significantly higher in active fighters compared with retired fighters and controls (P < .0001). For instance, NFL concentrations were 40 percent higher in active fighters than in non-fighters.
• Concentrations of NFL (but not of tau) were correlated with the amount of self-reported sparring that participants had done in the two weeks before their blood sample was taken.
• Active fighters showed a significant increase in tau levels over time, and this increase in tau was associated with a 7 percent lower baseline thalamic volume on MRI, which Dr. Bernick characterized as “substantial.” NFL levels did not increase significantly over time in active fighters.

The findings in context

“These results suggest that higher plasma levels of both neurofilament light chain and tau may be associated with repetitive head trauma,” observes Dr. Bernick. “It appears that neurofilament light chain may be more sensitive to acute TBI while tau may be a better metric of cumulative damage over time.”

He notes that the study is preliminary and is limited by the self-reported nature of the data on recent sparring and the differences in age between active and retired fighters.

“We don’t yet know whether increasing levels of tau over time indicate a risk of long-term neurological decline,” Dr. Bernick says. “Longer follow-up is needed to address that question, along with replication in other cohorts. But measurement of these brain proteins might one day help us detect brain injury early, predict who will develop complications and better monitor brain injury over time.”